In 1866, Mendel described the rules of probability that govern the inheritance of simple genetic traits. He demonstrated that individuals who show no evidence of a disease can still be silent “carriers” of a disease mutation. The disease only appears in a child who inherits two defective copies of a particular gene from two parents who are carriers. Diseases and other traits inherited in this manner are referred to as Mendelian. Thousands of Mendelian diseases of metabolism and other physiological functions have been described in the medical literature.
Although each individual Mendelian disease mutation is relatively rare, they are cumulatively so common that nearly every human being is a earlier for at least one. Carrier testing can identify two potential parents who have the same mutation and thus have a 25% likelihood of transmitting the corresponding disease to their child.
The vast majority of heritable attributes that distinguish one person from another in morphology, physiology, disease resistance and susceptibility, and mental function result from complex interactions among multiple genes and non-gene loci. Therefore, in most cases, the likelihood that two healthy parents will have a child with genetically-influenced health problems cannot be determined by simply comparing the carrier status of each individual since carrier status has no meaning in the context of a complex genetic trait.
Over the last decade, a pair of conceptual and technological breakthroughs has revolutionized the practice and potential of human genetic analysis. The conceptual breakthrough emerged from the discovery that most genetic variations in the global human population are confined to a limited number of chromosomal positions where one of two letters in the DNA alphabet can occur. These variant genomic positions are called single nucleotide polymorphism (“SNP”) loci.
The SNP conceptual breakthrough alone would not have been enough to transform human genetics if the process of determining DNA genotypes remained as tedious as it had been just a few years earlier. But high complexity DNA microarrays allowed the development of a technology for cheaply screening increasingly large numbers of SNPs or CNPs at ever-lower costs. A current state-of-the-art DNA microarray can assay over two million genotypes in an individual human genome.
Advances in DNA microarray design have enabled the detection of many types of characterized genetic variants. Whether simple or complex, most types of genetic variants can be defined in molecular terms as unique SNPs or CNPs for the purpose of analysis.
The ultimate description of a genome is its two 3 billion base pair long DNA sequences. The cost of obtaining a complete personal genome sequence is dropping rapidly. Scientists predict that it will become affordable to average consumers within a few years.
High complexity DNA microarray technologies, high throughput whole genome sequencing, and accompanying information technologies have revolutionized the field of human genetics, with extraordinary advances in understanding the genetic basis for complex traits and an enormous depth of public-access genetic datasets that increase in size daily.
Among other recent advances, scientists can now use cost-effective tools to analyze a patient's genome and predict susceptibility to thousands of medical conditions, including mental illness, neurological diseases, cancer, stroke and heart disease.
While progress has been made in developing computational tools that use information from an individual's genome to predict the likelihood of disease for that person, these tools cannot be applied to the pre-conception prediction of disease in a person's child. Thus, there is a need for methods of assessing the inheritance of such complex attributes prior to, or in place of, conception.